Synthesis and SAR studies of biaryloxy-substituted triazoles as antifungal agents

Bioorg Med Chem Lett. 2008 Jun 1;18(11):3261-5. doi: 10.1016/j.bmcl.2008.04.056. Epub 2008 Apr 25.

Abstract

A series of 1-(substituted biaryloxy)-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-1-yl) propan-2-ol were synthesized and their antifungal activities were evaluated against eight human pathogenic fungi in vitro. Seventeen compounds showed activity 4- to 64-fold higher than voriconazole against Candida albicans. SAR clearly suggested that introduction of a biaryloxy side chain greatly enhanced the antifungal activity of triazole analogs against Candida species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / chemical synthesis*
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Candida albicans / drug effects
  • Fluconazole / pharmacology
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Pyrimidines / pharmacology
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry
  • Triazoles / pharmacology*
  • Voriconazole
  • Yeasts / drug effects

Substances

  • Antifungal Agents
  • Pyrimidines
  • Triazoles
  • Fluconazole
  • Voriconazole